Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OT5F6LUP)

• DOT Name: PHD finger protein 11 (PHF11)
• Synonyms: BRCA1 C-terminus-associated protein; Renal carcinoma antigen NY-REN-34
• Gene Name: PHF11
• Related Disease:
  Cockayne syndrome type 1
  Allergic asthma
  Allergic rhinitis
  Asthma
  Atopic dermatitis
  Bacillary dysentery
  Ewing sarcoma
  Keratoconjunctivitis
  Malignant soft tissue neoplasm
  Sarcoma
• UniProt ID: PHF11_HUMAN
• Pfam ID: PF13771
• Sequence:
  MAQASPPRPERVLGASSPEARPAQEALLLPTGVFQVAEKMEKRTCALCPKDVEYNVLYFA
  QSENIAAHENCLLYSSGLVECEDQDPLNPDRSFDVESVKKEIQRGRKLKCKFCHKRGATV
  GCDLKNCNKNYHFFCAKKDDAVPQSDGVRGIYKLLCQQHAQFPIIAQSAKFSGVKRKRGR
  KKPLSGNHVQPPETMKCNTFIRQVKEEHGRHTDATVKVPFLKKCKEAGLLNYLLEEILDK
  VHSIPEKLMDETTSESDYEEIGSALFDCRLFEDTFVNFQAAIEKKIHASQQRWQQLKEEI
  ELLQDLKQTLCSFQENRDLMSSSTSISSLSY
• Function: Positive regulator of Th1-type cytokine gene expression.
• Tissue Specificity: Highly expressed in T and B-cells, as well as natural killer and mature dendritic cells. Expressed at higher levels in Th1 as compared to Th2 cells. Expressed at low levels in all normal tissues tested, including lung, testis, small intestine, breast, liver and placenta.

Molecular Interaction Atlas (MIA) of This DOT

10 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Cockayne syndrome type 1	DIS9JFVY	Definitive	Biomarker	[1]
Allergic asthma	DISHF0H3	Strong	Genetic Variation	[2]
Allergic rhinitis	DIS3U9HN	Strong	Biomarker	[3]
Asthma	DISW9QNS	Strong	Biomarker	[4]
Atopic dermatitis	DISTCP41	Strong	Genetic Variation	[5]
Bacillary dysentery	DISFZHKN	Strong	Biomarker	[6]
Ewing sarcoma	DISQYLV3	Strong	Biomarker	[7]
Keratoconjunctivitis	DISOYCQC	Strong	Genetic Variation	[6]
Malignant soft tissue neoplasm	DISTC6NO	Strong	Biomarker	[8]
Sarcoma	DISZDG3U	Strong	Biomarker	[8]

14 Drug(s) Affected the Gene/Protein Processing of This DOT

Drug Name	Drug ID	Highest Status	Interaction	REF
Valproate	DMCFE9I	Approved	Valproate decreases the expression of PHD finger protein 11 (PHF11).	[9]
Ciclosporin	DMAZJFX	Approved	Ciclosporin increases the expression of PHD finger protein 11 (PHF11).	[10]
Tretinoin	DM49DUI	Approved	Tretinoin increases the expression of PHD finger protein 11 (PHF11).	[11]
Acetaminophen	DMUIE76	Approved	Acetaminophen decreases the expression of PHD finger protein 11 (PHF11).	[12]
Doxorubicin	DMVP5YE	Approved	Doxorubicin decreases the expression of PHD finger protein 11 (PHF11).	[13]
Cupric Sulfate	DMP0NFQ	Approved	Cupric Sulfate affects the expression of PHD finger protein 11 (PHF11).	[14]
Temozolomide	DMKECZD	Approved	Temozolomide decreases the expression of PHD finger protein 11 (PHF11).	[15]
Vorinostat	DMWMPD4	Approved	Vorinostat decreases the expression of PHD finger protein 11 (PHF11).	[16]
Demecolcine	DMCZQGK	Approved	Demecolcine increases the expression of PHD finger protein 11 (PHF11).	[17]
Urethane	DM7NSI0	Phase 4	Urethane decreases the expression of PHD finger protein 11 (PHF11).	[18]
PMID28460551-Compound-2	DM4DOUB	Patented	PMID28460551-Compound-2 decreases the expression of PHD finger protein 11 (PHF11).	[21]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A decreases the expression of PHD finger protein 11 (PHF11).	[22]
Trichostatin A	DM9C8NX	Investigative	Trichostatin A increases the expression of PHD finger protein 11 (PHF11).	[23]
Formaldehyde	DM7Q6M0	Investigative	Formaldehyde increases the expression of PHD finger protein 11 (PHF11).	[17]

2 Drug(s) Affected the Post-Translational Modifications of This DOT

Drug Name	Drug ID	Highest Status	Interaction	REF
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene increases the methylation of PHD finger protein 11 (PHF11).	[19]
TAK-243	DM4GKV2	Phase 1	TAK-243 increases the sumoylation of PHD finger protein 11 (PHF11).	[20]

References

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• [2] A role for the atopy-associated gene PHF11 in T-cell activation and viability.Immunol Cell Biol. 2010 Nov-Dec;88(8):817-24. doi: 10.1038/icb.2010.57. Epub 2010 Apr 27.
• [3] Genome-wide association study for atopy and allergic rhinitis in a Singapore Chinese population.PLoS One. 2011;6(5):e19719. doi: 10.1371/journal.pone.0019719. Epub 2011 May 20.
• [4] Allele-specific transcription of the asthma-associated PHD finger protein 11 gene (PHF11) modulated by octamer-binding transcription factor 1 (Oct-1).J Allergy Clin Immunol. 2011 Apr;127(4):1054-62.e1-2. doi: 10.1016/j.jaci.2010.12.015. Epub 2011 Feb 12.
• [5] Functional characterization of the atopy-associated gene PHF11.J Allergy Clin Immunol. 2008 May;121(5):1148-1154.e3. doi: 10.1016/j.jaci.2008.02.028. Epub 2008 Apr 11.
• [6] Alteration in apyrase enzyme attenuated virulence of Shigella flexneri.Microb Pathog. 2016 Feb;91:123-8. doi: 10.1016/j.micpath.2015.12.004. Epub 2015 Dec 17.
• [7] Functional epigenetic approach identifies frequently methylated genes in Ewing sarcoma.Epigenetics. 2013 Nov;8(11):1198-204. doi: 10.4161/epi.26266. Epub 2013 Sep 4.
• [8] Anti-tumor and immunomodulatory activities induced by an alkali-extracted polysaccharide BCAP-1 from Bupleurum chinense via NF-B signaling pathway.Int J Biol Macromol. 2017 Feb;95:357-362. doi: 10.1016/j.ijbiomac.2016.10.112. Epub 2016 Nov 22.
• [9] Human embryonic stem cell-derived test systems for developmental neurotoxicity: a transcriptomics approach. Arch Toxicol. 2013 Jan;87(1):123-43.
• [10] Integrating multiple omics to unravel mechanisms of Cyclosporin A induced hepatotoxicity in vitro. Toxicol In Vitro. 2015 Apr;29(3):489-501.
• [11] Development of a neural teratogenicity test based on human embryonic stem cells: response to retinoic acid exposure. Toxicol Sci. 2011 Dec;124(2):370-7.
• [12] Gene expression analysis of precision-cut human liver slices indicates stable expression of ADME-Tox related genes. Toxicol Appl Pharmacol. 2011 May 15;253(1):57-69.
• [13] Bringing in vitro analysis closer to in vivo: studying doxorubicin toxicity and associated mechanisms in 3D human microtissues with PBPK-based dose modelling. Toxicol Lett. 2018 Sep 15;294:184-192.
• [14] Physiological and toxicological transcriptome changes in HepG2 cells exposed to copper. Physiol Genomics. 2009 Aug 7;38(3):386-401.
• [15] Temozolomide induces activation of Wnt/-catenin signaling in glioma cells via PI3K/Akt pathway: implications in glioma therapy. Cell Biol Toxicol. 2020 Jun;36(3):273-278. doi: 10.1007/s10565-019-09502-7. Epub 2019 Nov 22.
• [16] Gene microarray analysis of human renal cell carcinoma: the effects of HDAC inhibition and retinoid treatment. Cancer Biol Ther. 2008 Oct;7(10):1607-18.
• [17] Characterization of formaldehyde's genotoxic mode of action by gene expression analysis in TK6 cells. Arch Toxicol. 2013 Nov;87(11):1999-2012.
• [18] Ethyl carbamate induces cell death through its effects on multiple metabolic pathways. Chem Biol Interact. 2017 Nov 1;277:21-32.
• [19] Air pollution and DNA methylation alterations in lung cancer: A systematic and comparative study. Oncotarget. 2017 Jan 3;8(1):1369-1391. doi: 10.18632/oncotarget.13622.
• [20] Inhibiting ubiquitination causes an accumulation of SUMOylated newly synthesized nuclear proteins at PML bodies. J Biol Chem. 2019 Oct 18;294(42):15218-15234. doi: 10.1074/jbc.RA119.009147. Epub 2019 Jul 8.
• [21] Cell-based two-dimensional morphological assessment system to predict cancer drug-induced cardiotoxicity using human induced pluripotent stem cell-derived cardiomyocytes. Toxicol Appl Pharmacol. 2019 Nov 15;383:114761. doi: 10.1016/j.taap.2019.114761. Epub 2019 Sep 15.
• [22] Gene expression profiling in Ishikawa cells: a fingerprint for estrogen active compounds. Toxicol Appl Pharmacol. 2009 Apr 1;236(1):85-96.
• [23] From transient transcriptome responses to disturbed neurodevelopment: role of histone acetylation and methylation as epigenetic switch between reversible and irreversible drug effects. Arch Toxicol. 2014 Jul;88(7):1451-68.